Mitochondrial quality control plays an important role in maintaining homeostasis of mitochondrial network and normal function of mitochondria. ATPase family AAA domain-containing protein 3A (ATAD3A) is one of the mitochondrial membrane proteins involved in the regulation of mitochondrial structure and function, mitochondrial dynamics, mitophagy and other important biological processes. Recent studies show that ATAD3A not only interacts with Mic60/Mitofilin and mitochondrial transcription factor A (TFAM) to maintain mitochondrial cristae morphology and oxidative phosphorylation, but also interacts with dynamin-related protein 1 (Drp1) to positively/negatively regulate mitochondrial fission. In addition, ATAD3A serves as a bridging factor between the translocase of the outer mitochondrial membrane (TOM) complex and translocase of the inner mitochondrial membrane (TIM) complex to facilitate the import of PTEN-induced putative kinase protein 1 (PINK1) into mitochondria and its processing displays a pro-autophagic or anti-autophagic activity. This article reviews the role and mechanism of ATAD3A in regulating mitochondrial quality control. Firstly, as an inner mitochondrial membrane protein, ATAD3A is involved in maintaining the stability of mitochondrial crista structure, and its gene deletion or mutation will cause the loss and breakage of crista. Secondly, ATAD3A is also involved in maintaining mitochondrial respiratory function and mitochondrial nucleoid homeostasis, and its gene deletion or mutation can reduce the activity of mitochondrial respiratory chain complex and enhance the size and movement of nucleoid. Thirdly, ATAD3A participates in the negative regulation of mitochondrial fusion, but its role in mitochondrial fission may dependent on specific cell types, as it can promote and/or inhibit the mitochondrial fission by increasing and/or decreasing phosphorylation or oligomerization of Drp1. Finally, ATAD3A can interact with mitophagy-related proteins (e.g. PINK1, autophagy/beclin-1 regulator 1 (AMBRA1), acylglycerol kinase (AGK)) to enhance/reduce PINK1-Parkin-dependent mitophagy.

Objective To explore the effect of 4-week repetitive downhill treadmill running on the mi-tochondrial structure,function,and autophagy in skeletal muscle of rats,so as to analyze the role of FKBP8-mediated mitophagy in exercise-induced mitochondrial damage in their skeletal muscles.Meth-ods Thirty-two male adult Sprague-Dawley rats were randomly divided into a 2-week quiet control group(2C group,n=8),a 4-week quiet control group(4C group,n=8),a 2-week exercise group(2E group,n=8)and a 4-week exercise group(4E group,n=8).Rats in 2E and 4E groups performed dai-ly 90-minute downhill treadmill running(-16°,16 m/min)5 days a week for two and four weeks,re-spectively.Then,they rested for 24 hours and received an exhaustive exercise test.Running distance and blood lactate were measured prior to and at the time of exercise cessation.Moreover,mitochondri-al ultrastructural changes in soleus muscles were observed by using a transmission electron microscope.The protein expression of mitochondrial succinate dehydrogenase subunit B(SDHB),cytochrome C oxi-dase subunit 1(MTCO1),FK506 binding protein 8(FKBP8)and microtubule associated protein 1 light chain 3(LC3)in the soleus muscle were measured using Western blotting.Meanwhile,the co-localiza-tion of FKBP8 with LC3 and cytochrome C oxidase subunit Ⅳ(COXⅣ)with LC3,lysosomal associat-ed membrane protein 2(LAMP2)were detected by the immunofluorescence double labeling technique.Results(1)The running distance of one exhaustive exercise and the blood lactate before and after the test in 2E group were significantly higher than 2C and 4E groups(P<0.05 or P<0.01),and the run-ning distance of 4E group was significantly higher than 4C group(P<0.01).However,there was no sig-nificant difference between 4E and 4C groups in the blood lactate before and after the exhaustive exer-cise test(P>0.05).(2)In both 2E and 4E groups,significant mitochondrial swelling and accumulation under cell membrane,as well as a number of mitophagosomes and mitophagolysosomes were observed,together with a significant reduce in the number of mitochondria(P<0.05),which was more severe in 2E group than 4E group.(3)The protein expression of mitochondrial SDHB and MTCO1 in 2E and 4E groups were lower than 2C and 4C groups,respectively,with significantly greater changes of these proteins in 4E group than 2E group(P<0.05 or P<0.01).(4)The protein expression of mitochondrial FKBP8 and LC3,as well as the co-localization of FKBP8 with LC3 and COXⅣ with LC3,LAMP2 in 2E and 4E groups were higher than 2C and 4C groups,respectively,with significantly greater changes in 4E group than 2E group(P<0.05 or P<0.01).Conclusion After 4-week downhill treadmill running,the structure,quantity and function of mitochondria in skeletal muscle are impaired.FKBP8-mediated mitophagy is activated,but is insufficient to degrade the damaged mitochondria,leading to muscular damage,as well as the increasing and falling down of running capacity.

OBJECTIVE: To evaluate the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy for patients with Ornithine transcarbamylase deficiency (OTCD). METHODS: Two children with OTCD were selected as the study subjects, and their clinical manifestations, blood ammonia, liver enzymes, growth and development information following the treatment with GPB were retrospectively analyzed. A literature review was also carried out by searching the PubMed database for studies on the GPB treatment for urea cycle disorders. RESULTS: With the GPB treatment, the blood ammonia and liver enzyme level in both patients have decreased to the normal range within 3 months. Motor development in child 2 has improved. No adverse reaction was noted, except for transient palmar greasy smell and loss of appetite in child 1. Analysis of the literature showed that patients had lower ammonia exposure, lower annual incidence of hyperammonemic crisis, more actual protein intake and fewer adverse events during GPB treatment. CONCLUSION GPB is safe and effective for the treatment of OTCD.
Child ; Humans ; Ornithine Carbamoyltransferase Deficiency Disease/drug therapy* ; Phenylbutyrates/therapeutic use* ; Ammonia ; Retrospective Studies

【Objective】 To investigate the effects of preoperative ureteroscopy (URS) on the intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). 【Methods】 The clinical data of 241 UTUC patients treated during May 2012 and Jan.2020 in the Second Hospital of Laozhou University were retrospectively analyzed. The patients were divided into URS before RNU group (URS group) and non-URS before RNU group (non-URS group). The cumulative IVR rate, progression-free survival (PFS) and overall survival (OS) after RNU were compared, and the survival curve was drawn. Cox proportional hazards models were used to assess risk factors affecting IVR. 【Results】 Of the 241 patients, 64 (26.6%) were included in the URS group and 177 (73.4%) in the non-URS group. In the URS group, 49 underwent biopsy and 15 did not. All patients were followed up for a median of 44 (3 to 122) months, with a median time to recurrence of 12 (3 to 56) months. IVR occurred in 18 patients (28.1%) in the URS group and 25 (14.1%) in the non-URS group. Kaplan-Meier survival analysis showed that the cumulative IVR rate was higher in the URS group than in the non-URS group (all P<0.05), regardless of whether patients had a history of bladder cancer (BC) or not, while PFS was lower in the URS group than in the non-URS group (P=0.007). Cox multivariate regression analysis showed that URS (P=0.031) and complicated renal pelvis tumor and ureteral tumor (P=0.004) were independent risk factors for IVR. 【Conclusion】 Preoperative URS increases the incidence of IVR in patients with UTUC, and routine preoperative use of URS is not recommended.

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Fibroma/diagnostic imaging* ; Humans ; Odontogenic Tumors/diagnostic imaging* ; Tuberous Sclerosis/complications*

Solitary fibroma often occurs in the pleura, but rarely outside the pleura. Extrapleural solitary fibroma has atypical clinical symptoms and difficult imaging diagnosis. Here, we report a case of solitary fibroma recurred and metastasized to the bladder after pelvic surgery. He was treated with palliative resection in our hospital. The patient died of systemic metastasis 3 years after operation.

Objective: To explore the association between inflammation activity of left atrial epicardial adipose tissue (LA-EAT) measured by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and atrial fibrillation (AF). Methods: A total of 78 patients with AF, who underwent ¹⁸F-FDG PET/CT in the Nuclear Medicine Department of the Third Affiliated Hospital of Soochow University due to abnormally elevated levels of tumor indicators or malignant tumors from March 2018 to December 2019, were enrolled in this retrospective study. According to the examination date of PET/CT and basic characteristics of AF patients (gender, age), a 1∶1 propensity score matching was used to enroll a non-AF control group (78 patients). The maximum standard uptake value of left atrial epicardial tissue (LA-EAT FDG SUV_max) and total EAT volume (V-EAT) were measured by ¹⁸F-FDG PET/CT. Left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) were obtained by echocardiography. Blood lipids and biomarkers of inflammation were measured. The differences of clinical data and EAT-related indicators were compared between the AF group and control group. Logistic multivariate regression analysis was used to determine the related factors of AF. Then the receiver operating characteristic (ROC) curve was used to determine the cutoff value of LA-EAT FDG SUV_max on the diagnosis of AF. Univariate and multivariate logistic regression analysis were used to analyze the relationship between the increase of LA-EAT FDG SUV_max and AF. Results: The age was (66.9±10.2) years and there were 55 males (70.5%) in the AF group. The age was (66.9±8.0) years, and there were 52 males (66.7%) in the control group (both P>0.05). The LAD ((44.2±5.8) mm vs. (35.4±4.4) mm), V-EAT ((122.1±42.0) cm³ vs. (91.6±34.5) cm³), and LA-EAT FDG SUV_max ((1.6±0.3) vs. (1.4±0.2)) values were significantly higher, while LVEF ((60.1±4.7)% vs. (63.9±2.9)%) was lower in the AF group than in the control group (P all<0.001). Multivariate logistic regression analysis showed that LAD (OR=1.340, 95%CI 1.195-1.502), V-EAT (OR=1.016, 95%CI 1.001-1.031), and LA-EAT FDG SUV_max (OR=1.375, 95%CI 1.095-1.723) were positively correlated with AF, LVEF (OR=0.781, 95%CI 0.659-0.926) was negatively correlated with AF(P all<0.05). The area under the ROC curve of LA-EAT FDG SUV_max for diagnosis of AF was 0.680 (95%CI 0.597-0.764, P<0.001), and the best cut-off value was 1.415 with a sensitivity of 65.4% and specificity of 61.5%. After adjusting for high-density lipoprotein cholesterol, LVEF, LAD and V-EAT, LA-EAT FDG SUV_max≥1.415 was independently associated with AF (OR=2.982, 95%CI 1.122-7.926, P=0.010). Conclusions: The inflammatory activity of LA-EAT measured by ¹⁸F-FDG PET/CT is an independent risk factor of AF, and the increased inflammatory activity of LA-EAT is positively correlated with AF.
Adipose Tissue/diagnostic imaging* ; Aged ; Atrial Fibrillation/diagnostic imaging* ; Fluorodeoxyglucose F18 ; Humans ; Inflammation/diagnostic imaging* ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

Radical nephroureterectomy with bladder cuff resection is the gold standard for the treatment of high-grade upper tract urothelial carcinoma. Due to the multicenter characteristics of urothelial carcinoma, 22% to 47% of patients still have bladder tumor recurrence after operation. A series of randomized controlled trials have shown that postoperative intravesical chemotherapy can effectively reduce the intravesical recurrence rate after operation. At present, postoperative intravesical instillation treatment and drugs still refer to bladder urothelial carcinoma, and the standard treatment has not been established yet. This article reviews the relevant literature in recent years, and systematically discusses the research development of postoperative intravesical chemotherapy in terms of the choice of chemotherapy protocol and drugs.

Objective To examine the expression and analyze the significance of autophagy-related gene microtubule-associated protein 1 light chain 3 (MAP1-LC3,LC3),p62 and lysosorne-associated membrane protein 2 (LAMP-2) in pancreatic tissues of mice with acute pancreatitis (AP).Methods Twenty mice were randomized into AP group and control group,and the number of mice was equal between two groups.AP group was intra-peritoneally injected by 20％ L-arginine solution (two injections of 4 g/kg body weight,every 1 h) in the dosage of 4 g/l kg twice every 1 hour to establish AP model,while control group was administered with equal volume of normal saline by intra-peritoneal injection.All the mice were euthanized at 24 hour after the last injection.Pancreatic histopathological changes were measured.In addition,the protein expressions of LC3,p62 and LAMP-2 were detected by Western blot.Results No obvious pathological changes were observed in control group.Pancreatic acinar edema,structure destruction,missing,the obvious widening of interlobular septum,small interlobular septum and acinar septum,and the necrosis of acinar cells at different degrees were observed in AP group.The pathological score for tissue edema,hemorrhage,necrosis and inflammation in AP group was 3.13 ± 0.50,2.83 ± 0.32,3.25 ± 0.46 and 3.16 ± 0.47,respectively,which was all 0 in control group.The differences were statistically significant between AP group and control group (P ＜ 0.01).In AP group,the ratio of LC3-Ⅱ/LC3-Ⅰ,p62 and LAMP-2 protein in pancreatic tissue were 1.16 ± 0.08,0.94 ± 0.04 and 0.35 ± 0.04,respectively,which were 0.24 ± 0.02,0.34 ± 0.03 and 0.95 ± 0.03 in control group.The ratio of LC3-Ⅱ/LC3-Ⅰ and p62 protein in pancreatic tissue in AP group were much higher than those in control group,while LAMP-2 in AP group was lower than that in control group,and there was statistically significant difference between two groups (all P ＜0.01).Conclusions Intraperitoneal injection of L-arginine could induce acute pancreatitis,and autophagy is impaired,which was associated with decreased LAMP-2 protein expression.